Sequencing Considerations and Elderly Patient Data in CLL

Dr. Shadman introduces an important practical consideration from Flatiron real-world data examining BTKi discontinuation rates in elderly patients, challenging the notion that older patients with CLL need only one line of therapy.

The analysis stratified patients into age groups of 75 to 79 years and 80 years and older, examining first-line therapy discontinuation rates. Dr. Lipsky explains this tracks with reasoning from first principles, given expected median PFS on zanubrutinib extending beyond 9 to 10 years, meaningful proportions of even elderly patients will live long enough to require subsequent therapy.

With 75- to 79-year-old patients, approximately half required a subsequent line of therapy during follow-up. For patients aged 80 and older, approximately one-third required additional treatment. Dr. Lipsky emphasizes that this data reinforces the need to consider long-term sequencing even for elderly patients, informing initial conversations at treatment start about anticipated therapy duration, sequential lines, and what options will be available at progression.

The discussion transitions to practical decision-making for BTKi selection between acalabrutinib and zanubrutinib. The ALPINE study demonstrated an efficacy advantage for zanubrutinib. The ELEVATE-RR study comparing acalabrutinib and ibrutinib used a different design without demonstrating an efficacy improvement but confirmed acalabrutinib's favorable safety profile. Dr. Shadman notes he discusses both studies with patients alongside safety profiles to reach individualized decisions, and very rarely needs to invoke indirect comparisons or real-world evidence in routine clinical practice, viewing these primarily as academic confirmatory data.